High resolution mass spectrometry for studying the interactions of cisplatin with oligonucleotides.
Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has been used to probe the interaction of the anticancer drug cisplatin with oligonucleotides. The binding kinetics, the nature of the adducts formed, and the location of the binding site within the specifically designed double-stranded DNA oligonucleotides, ds(GTATTGGCACGTA) and ds(GTACCGGTGTGTA), were determined by recording mass spectra over time and/or employing tandem mass spectrometry (MS/MS). The FT-ICR MS studies show that binding to DNA takes place via a [Pt(NH 3) 2Cl] (+) intermediate prior to formation of bifunctional [Pt(NH 3) 2] (2+) adducts. Tandem MS reveals that the major binding sites correspond to GG and GTG, the known preferred binding sites for cisplatin, and demonstrates the preference for binding to guanosine within the oligonucleotide. The obtained results are discussed and compared to published data obtained by other mass spectrometric techniques, NMR spectroscopy and X-ray crystallography.
Egger
Alexander E
AE
University of Vienna, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria.
Hartinger
Christian G
CG
Ben Hamidane
Hisham
H
Tsybin
Yury O
YO
Keppler
Bernhard K
BK
Dyson
Paul J
PJ
D001665:Binding Sites; D002945:Cisplatin / Q000737:chemistry*; D018360:Crystallography, X-Ray; D018736:DNA Adducts / Q000737:chemistry*; D005583:Fourier Analysis; D007700:Kinetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009841:Oligonucleotides / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D018736:DNA Adducts; D009841:Oligonucleotides; C057270:cisplatin-DNA adduct; D002945:Cisplatin